Nu-alkyl thiamorpholines and derivatives



Patented Apr. 13, 1948 N-ALKYL THIAMOBPHOLINES AND DERIVATIVES Joseph B.Niederl, Brooklyn, N. Y., and William F. Hart, Easton, Pa.

No Drawing. Application May 3, 1945, Serial No. 591,850

4 Claims. (01. 260-243) 1 2 This invention relates to the utilization ofa N-alkyl-thiamorpholine-l-oxides: war gas, di-(fi-chloro-ethyl) sulfide(mustard 2HCl as), and its oxidation products in the manu- (0103103989"'f PNwmcmhso facture of useful products, such products finding'N'alkyl-thlamorphohhe-l-dloxldes1 application as anti-oxidants, asdetergents, wet- ENE (CICHZCHQSOZ IPMCHZCHMSO ting and flotation agents,as well as bactericides, The tertiary amine Salts [zwHzcHznNmHx]fungicides and antiseptics.

of the foregoing compounds are prepared by More partlculafly thlsInvention relates to the treating the free bases with mineral or with orpreparation from mustard gas of N-alkyl thimor- I ganic acids, while thequaternary ammonium $31 3 5; l l i o ifgt l fid o i fiafil yffih faggfisalts [ZtCHzCHz)2NR(R/)Xl are prepared by the pholine oxides anddioxides in which the alkyl Interact)? the m f bases 3 alkyl radicalcontains the same number of carbon gi g ifgffgs fiit g figi b zi ggesters atoms, and which are prepared from the oxidation products ofmustard gas, di-(p-chloro-ethyl) xample 1.N-cetyl ihwmorpholme sulfoxideand di-(B-chloro-ethyl) sulfone. seventy-six grams of cetyl amine (B. P.325

This invention also relates to the derivatives of meow are dissolved in120 of absolute 1- such long chain substituted thiamorpholines, 601101and 34 of anhydrous Sodium carbonate thiamorpholine-oxides and.thiamorpholine-diaddedgrams of mustard gas are then Oxides in Which thenitrogen atom may not only added, and the solution refluxed for eighthours. be trivalent but a so pentwvalent. Such The warm solution isfiltered to remove inorpounds having proven to be surface active agents.m salts, which are washed twice with hot The Various types of compoundsInvolved in thls absolute alcohol. The combined alcohol extracts inv maybe eXpressed by the followmg are distilled in vacuo to remove thesolvent. The eral formula: residue is then taken up in an excess of dryether, onion, and saturated with dry hydrogen chloride. The

hydrochloride is filtered ofl and washed repeat- \CH2C/h edly with d yether and with acetone. The free base is obtained by taking up thehydrochloride In the above general f a. Z r pr $111- in a concentratedpotassium hydroxide solution a dB, or a sulfone group. While Y andextracting Withether. The combined ether represents: extracts are driedover solid potassium hydroxide pellets, and the solvent removed bydistillation. or NR(R )X The free base is purified by recrystallizationfrom N being nitrogen, R a long chain alkyl radical of acetone from 12to 18 car on atoms, a Short Cham Substitution in the above procedure ofthe cetyl alkyl a yl rad cal, and X an an o amine by appropriate amountsof other long In preparing the compounds enumerated ahove, chain primaryamines, such as dodecyl-, tridecyb, mustard gas, or its Oxi atio P t ltetradecyl-, peta'decyl-, hept-adecyior octadecyl c o yl) sulfoxide orslllfonel, 1S reactefi 40 amines, produces the respective N-alkylthiamorwith l chain P y amlhes (dodecyl'w pholines, the physical andchemical properties of q w i e penta-decyh, hexa'decyl" some of whichare summarized below. hepta-decy1-, or octa-decylamine) to yield therespective long chain substituted N-alkyl thia- M P 00 C MRHYdmmorpholine, N-alkyl thiamorphohne-oxide and chloride N-alkylthiamorpholine-dioxide in accordance Win i n 2 N-Dodecyl-thiamor h l'159 wlth the 0110 g equat o s lg-getraiecyll-tigillam orgfii gllgne 15;

-31]; exa ecyamorp ome 162 N yl thiamorphonnes' H01N-Octadecyl-thiamorplioline 131 173 --2 ENE: +(c1cmcrms rpmcmcmns 0Example 2.--N-cetyZ-thiamorphoZine-I-o:cide

Fifty-five grams of cetyl amine (B. P. 325 C. (uncor.) and forty gramsof di-(s-chloro-ethyl) sulfoxide (M. P. 109) are dissolved in 500 cc. of95% alcohol and 24.1 grams of powdered anhydrous sodium carbonate areadded. The reaction mixture is refluxed for three hours and the hotsolution is filtered to remove inorganic salts, washing twice with hotalcohol. The product crystallizes in quite pure form, which may befurther purified by a re-crystallization from alcohol.

The hydrochloride is prepared by dissolving the product in dry benzeneand passing in dry hydrogen chloride gas, and purified byre-crystallization from benzene or alcohol, and finally washing with dryacetone.

Substitution in the above procedure of the cetyl amine by appropriateamounts of other long chain substituted primary amines produces therespective N-alkyl-thiamorpholine-l-oxides, the physical and chemicalproperties of some of which are summarized below.

Example 3.N-cetyZ-thiamorpholine-Idioxide Fifty and five-tenths grams ofcetyl amine (B. P. 325 C. (uncor) and forty grams of di-(s-chloro-ethyl)sulfone are dissolved in 500 cc. of alcohol, and 22.2 grams of powderedanhydrous sodium carbonate is added. This reaction mixture is refluxedfor one hour, the warm solution filtered to remove inorganic salts, andthe salts washed twice with hot alcohol. The product crystallizes oncooling and may be further purified by one re-crystallization fromalcohol. The hydrochloride is prepared by dissolving the product in drybenzene and passing in dry hydrogen chloride gas. This may be furtherpurified by recrystallization from benzene or alcohol, finally washingwith dry acetone.

Again, substitution in the above procedure of the cetyl amine byappropriate amounts of other long chain primary amines produces therespective N-alkyl-thiamorpholine-l-dioxides, the physical and chemicalproperties of some of which are tabulated below:

M. P. Hydro- M. P. 0 C. chloride N-Dodecyl thiamorpholine-l-dioxide 73173 N -Tetradecyl-thiamorpholine-ldioxide 85 169N-Hexadecyl-thiamorpholine-lo e 88 160N-Octadecyl-thiamorpholine-ldioxide 92 151 Example 4.Quatemary ammoniumalkyl sulfates stroy any unreacted di-alkyl sulfate, and a littledecolorizing carbon. The solution is than filtered, and the methanolremoved by vacuum distillation. The product is taken up in the leastquantity of warm water. The products are usually crystallized iromconcentrated water solution and are washed with dry acetone alterfiltering and air drying.

These quaternary ammonium sulfates are soluble in water; theethosulfates are usually about two times soluble in water as therespective metho-sulfates. The physical properties 01 some of thesecapillary active substances are enumerated below.

M. P. C. N-cetyl-N-methyl-thiamorpholinium methosulfate 210 N -cetylN-methyl-thiamorpholinium-l -oxide methosulfate 222N-cetyl-N-methyl-thiamorpholinium-l-dioxide methosulfate N-oetyl-N-ethyl-thiamorpholinium ethosulfate 202 N-cetylN-ethyl-thiamorpholinium- -oxide ethosulfate 215 N-cetyl-N-ethyl-thiamorpholinium-l-dioxide ethosulfate 173 Example 5.--Quatemary ammonium halides The methiodides and ethiodides areprepared by refluxing for three hours the respectiveN-alkyl-thiamorpholines, N-alkyl-thiamorpholine-l-oxides, orN-alkyl-thiamorpholine-l-dioxides with a slight excess of methyl orethyl iodide, respectively. After refluxing, the excess alky iodide isallowed to evaporate or is removed by distillation under diminishedpressure. The residue is usually crystallized from hot ethyl acetate.

Refluxing of the above free bases with molar quantities of benzylchloride, or an alkyl bromide in toluene solution for six hours,produces the corresponding quaternary ammonium chlorides or bromides,respectively. The solvent is usually removed by distillation in vacuo,the residue is then washed with dry acetone and finally alsocrystallized from hot ethyl acetate.

Some or the quaternary ammonium halides produced by the above procedureare given below.

M. P. C. N cetyl N methyl thiamorpholinium iodide 224N-cetyl-N-methyl-thiamorpholinium-l-oxide iodide 234 N-cetyl-N-methylthiamorpholinium-1-dioxide iodide N-cetyl-N-ethyl-thiamorpholiniumiodide 205 N-cetyl N benzyl-thiamorpholinium chloride 166N-cetyl-N-n-propyl thiamorpholinium bromide 225 N cetyl Nbenzyl-thiamorpholinium bromide 198 Example 6.Double quaternary ammoniumsalts in which Z represents an atomic grouping selected from the classconsisting of S, 80, and 802, R an alkyl radical containing from 12 to18 carbon'atoms, R a short chain alkyl radical. x an anion.

2. Compounds of the general formula:

cmcm n in which It represents an alkyl radical containing from 12 to 18carbon atoms and R a short chain alkyl radical.

3, Compounds of the general formula:

onion, 3 OS\ 3 cmcfi. sum

6 in which It represents an alkyl radical containing from 12 to 18carbon atoms and R a short chain alkyl radical.

4. Compounds of the general formula:

CHICK! R O S\ (R' CHaCr 504K.

in which R represents an alkyl radical contain- 7 ing from 12 to 18carbon atoms and R a short chain alkyl radical.

JOSEPH B. NIEDERL. WILLIAM F. HART.

REFERENCES CITED The following references are of record in the flle ofthis patent:

UNITED STATES PATENTS 20 Number Name Date 2,001,584 Reed May 14, 19352,129,805 Wilson Sept. 18, 1988 2,295,504 Shelton Sept. 8, 1942- FOREIGNPATENTS Number Country Date 133,108 Great Britain Sept. 26, 1919 OTHERREFERENCES Journal of the American Chemical Society, vol.

66, pages 840-1.

Chemical Reviews, vol. 15 (1934), pages 452-460. Journal of the AmericanChemical Society, vol. 47 (1925). Pp. 2821-2831.

